The effect of cardiac resynchronisation therapy upgrade from right ventricular pacing on symptoms and functional clinical outcomes, results from the BUDAPEST-CRT Upgrade trial

Abstract Background Based on the results of the BUDAPEST-CRT Upgrade trial, in patients with intermittent or permanent right ventricular (RV) pacing and reduced left ventricular ejection fraction (HFrEF) upgrade to cardiac resynchronization therapy (CRT) reduces morbidity and mortality. Purpose Whether the substantial treatment effect of the CRT upgrade could also be detected in a better functional and exercise capacity is scarcely investigated. We examined the changes of the prespecified tertiary endpoints such as symptoms, quality of life (QoL), exercise capacity and natriuretic peptide measurement from baseline to 12 months. Methods In the BUDAPEST CRT Upgrade trial 360 HFrEF patients with a priorly implanted PM or ICD and >20% of RV pacing burden were randomly assigned to CRT-D upgrade (n=215) or ICD (n=145) in a 3:2 ratio. The prespecified tertiary endpoints were changes in quality of life measured by EQ-5D-3L, New York Heart Association (NYHA) functional class, 6-minute walk test (6-MWT), and NT-proBNP. When data of trial patients were unavailable due to death at 12 months, imputed values were used as 0 (6MWT) and 0 score (EQ-5D-3L) or a 5th grade (NYHA class). Responders were defined as >15% change of left ventricular end-systolic volume at 12 months. Results From baseline to 12 months, NYHA functional class improved in the CRT-D upgrade arm compared with the ICD only group [adjusted odds ratio (OR) 0.50; 95% CI 0.32-0.80; P=0.003]. According to the adjusted model there was a statistically significant decrease in the NT-proBNP [adjusted difference -1257 pg/mL; 95% CI -2287 – (-228); P=0.017]. In responders, the changes in NT-proBNP levels were significantly greater than in non-responders [adjusted difference -1635 pg/mL; 95% CI -2811 - (-459); P=0.007]. The progression of worsening of QoL attributed to ageing was moderated only by CRT-D upgrade [EQ-5D-3L difference by age -0.01; 95% CI -0.02 - (-0.003); P=0.004; interaction P=0.003]. 6MWT did not improve significantly in either group. Conclusions Patients receiving CRT upgrade showed a substantial improvement in symptoms and a significant decrease in natriuretic peptide levels, as compared to ICD alone, which was more pronounced in responders. Moreover, CRT-D upgrade could moderate the progression of worsening of quality of life attributed to ageing in this vulnerable, older patient population.